Overexpression of fibroblast growth factor receptors FGFR1 and FGFR2 in renal cell carcinoma.

OBJECTIVE

Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) has recently emerged as a critical event in the transformation and tumorigenicity of several murine and human tumors. This pathway could be a mechanism driving angiogenesis in patients with metastatic renal cell carcinoma (RCC). Membrane antigens such as FGFR expressed in RCC are attractive targets for new therapeutic and diagnostic applications. This study evaluated the expression of FGFR1 and FGFR2 in RCC.

MATERIAL AND METHODS

Formalin-fixed, paraffin-embedded specimens of 100 primary tumors and 40 metastatic lymph nodes removed from 140 untreated RCC patients were evaluated by immunohistochemistry with FGFR1 and FGFR2 antibodies. The extent of FGFR expression was compared with 40 specimens of normal human kidney tissue (selected from the surgical diagnostic files). Significant differences in the immunoexpression of FGFR among these groups were assessed bychi-squared and Fisher's exact tests using a semi-quantitative scoring system on the extent of stained cells and intensity of corresponding immunostained cells (0 to 3+).

RESULTS

Expression of FGFR1 was observed in 98% (98/100) of primary renal tumors and in 82.5% (33/40) of lymph-node metastases. Intensity was 3+ in allcases. Nuclear expression of FGFR1 was found in 68% (95/140). FGFR2 staining was seen in 4% (4/100) of primary tumors and in 5% (2/40) of lymph-node metastases. FGFR2 was expressed in RCC of non-clear cell histology. FGFR1 expression was significantly lower in the normal kidney tissue(p = 0.001) and was detected in 2.5% of cases (1/40); no FGFR2 expression was found.

CONCLUSION

This study has shown for the first time that FGFR1 is highly expressed in RCC patients.